Determining the optmal time for valve replacement surgery in patients with mitral regurgitation (MR) is an important clinical problem. Patients with few or no symptoms, despite severe mitral regurgitation, present a particular problem. Since some patients remain asymptomatic for 10-20 years, it would be unwise to subject a patient prematurely to an operation which has a high operative mortality (5-10%) or the risks of a prosthetic valve. On the other hand, waiting too long can increase the surgical mortality and jeopardize the postoperative effect, resulting in irreversible left ventricular dysfunction. This protocol was initiated by the Cardiology Branch in 1978 to study the natural history of two groups of patients with MR; those who were asymptomatic with those who were operative candidates. Invasive (cardiac catheterization and noninvasive (M-mode echo, stress tests and radionuclide angiography) parameters of LV function were performed in an effort to find an objective predictor of clinical deterioration. What is clear so far is by the time patients with MR become symptomatic enough to require operation, most have sustained left ventricular dysfunction which appears to be irreversible. Preoperative left ventricular dilatation by M-mode echo (LVDD greater than 70 or LVSD greater than 45) may identify patients at greater risk for severe postoperative LV dysfunction. The clinical significance of this depressed postoperative LV function remains to be determined by long-term follow-up studies. It is crucial that the nonoperated and the operated patients continue to have follow-up noninvasive studies to further determine what preoperative parameters influence post-operative clinical course and to prove the relationship of these findings to the natural history of MR patients postoperatively.